SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Banimax Tablets.

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Aspirin 250mg,

Paracetamol 250mg

3    PHARMACEUTICAL FORM

Bilayered tablet.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Banimax Tablets are indicated for the short term treatment of mild to moderate pain, for example that associated with headache, toothache or injury, and the symptomatic relief of febrile illnesses, such as upper respiratory infections and influenza.

4.2    Posology and method of administration

Method of administration: Oral

Adults: 2 tablets three to four times a day every 4 to 6 hours to a maximum of 8 tablets during any 24 hour period.

Elderly: A reduced dosage may be required see precautions and warnings.

Do not give to children under 16 years, unless specifically indicated (e.g. for Kawasaki’s disease).

The tablets should be swallowed whole and not broken or crushed.

4.3 Contraindications

Hypersensitivity to aspirin, paracetamol; and/or ingredients. Patients with asthma or allergic reactions to other non-steroidal anti-inflammatory drugs. Patients with active of chronic or recurrent gastric or duodenal ulcers with/without concomitant bleeding.

Patients with haemorrhagic disease such as haemophilia.

Patients with severe renal and liver disorders.

Apirin must not be given to children under 16 years of age.

The last 3 months of pregnancy.

4.4 Special warnings and precautions for use

Patients suffering from glucose-6-phosphate dehydrogenase deficiency. Banimax should not be used before or after dental extractions and it should not be taken before or after alcohol consumption.

Care is advised in the administration of Banimax to patients with severe renal disease. The hazards of overdosage are greater in those with alcoholic liver disease.

Do not exceed the stated dose.

Patients should be advised not to take other paracetamol or aspirin-containing products concurrently.

If symptoms persist consult your doctor.

Keep out of the reach of children.

There is a possible association between Aspirin and Reye’s Syndrome when administered to children. Reye’s Syndrome is a very rare disease which affects the brain and liver, and can be fatal. For this reason it should not be given to children under 16 years unless specifically indicated (e.g. for Kawasaki’s disease).

The label should contain the statement "do not give to children under 16 years of age, unless on the advice of a doctor”, “immediate medical advice should be sought in the event of an overdose, even if you feel well”, and “Do not take with any other paracetamol containing products”.

4.5 Interaction with other medicinal products and other forms of interaction

Banimax may potentiate:-

The action of anticoagulants, such as heparin and warfarin, increasing the risk of bleeding.

The risk of gastrointestinal bleeding during concomitant therapy with corticosteroids.

The effect of metoclopramide.

Anti-epileptic drugs such as phenytoin and sodium valproate.

The effects and side effects of other NSAID's.

The effects of oral anti-diabetic drugs.

The toxicity of methotrexate by inhibiting tubular secretion of the drug.

Banimax may reduce the action of :-Diuretics e.g. spironolactone and thiazides.

Uricosuria

Banimax excretion is increased by alkalinisation of urine.

The paracetamol component of this product may cause a marginal increase in blood levels of chloramphenicol.

The speed of absorption of the paracetamol component may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.

4.6 Pregnancy and lactation

As Banimax contains aspirin and paracetamol it should not be taken by pregnant women in the first and second trimester unless under medical supervision and only if the expected benefit to the mother is considered to be greater than the risk to the baby.

Banimax should not be taken in the last trimester of pregnancy and when breast feeding as the aspirin component impairs platelet function and increases the risk of haemorrhage to the baby e.g. intracranial haemorrhage. The aspirin component of Banimax may also cause delayed onset, and increased duration of labour, closure of foetal ductus arteriosus in utero and possibly persistent pulmonary hypertension of newborn; kernicterus in jaundiced neonates.

4.7 Effects on ability to drive and use machines

None stated.

4.8 Undesirable effects

Banimax may cause gastric irritation and dyspepsia. In some cases of intensive use gastric bleeding may occur.

Nausea and vomiting, diarrhoea, tinnitus, vertigo, mental confusion. There have been reports of blood disorder, in particular thrombocytopenia and more rarely, agranulocytosis and of acute pancreatitis.

Hypersensitivity reactions such as skin reactions, dyspnoea and bronchospasms. Rhinitis, angioedema, severe cutaneous skin eruptions have been reported and pre-orbital oedema may occur.

4.9 Overdose

Aspirin

Salicylate poisoning is usually associated with plasma concentrations >350 mg/L (2.5 mmol/L). Most adult deaths occur in patients whose concentrations exceed 700 mg/L (5.1 mmol/L). Single doses less than 100 mg/kg are unlikely to cause serious poisoning.

Symptoms:

Common features include vomiting, dehydration, tinnitus, vertigo, deafness, sweating, warm extremities with bounding pulses, increased respiratory rate and hyperventilation. Some degree of acid-base disturbance is present in most cases.

A mixed respiratory alkalosis and metabolic acidosis with normal or high arterial pH (normal or reduced hydrogen ion concentration) is usual in adults and children over the age of four years. In children aged four years or less, a dominant metabolic acidosis with low arterial pH (raised hydrogen ion concentration) is common. Acidosis may increase salicylate transfer across the blood brain barrier.

Uncommon features include haematemesis, hyperpyrexia, hypoglycaemia, hypokalaemia, thrombocytopaenia, increased INR/PTR, intravascular coagulation, renal failure and non-cardiac pulmonary oedema.

Central nervous system features including confusion, disorientation, coma and convulsions are less common in adults than in children.

Management:

Give activated charcoal if an adult presents within one hour of ingestion of more than 250 mg/kg. The plasma salicylate concentration should be measured, although the severity of poisoning cannot be determined from this alone and the clinical and biochemical features must be taken into account. Elimination is increased by urinary alkalinisation, which is achieved by the administration of 1.26% sodium bicarbonate. The urine pH should be monitored. Correct metabolic acidosis with intravenous 8.4% sodium bicarbonate (first check serum potassium). Forced diuresis should not be used since it does not enhance salicylate excretion and may cause pulmonary oedema.

Haemodialysis is the treatment of choice for severe poisoning and should be considered in patients with plasma salicylate concentrations >700 mg/L (5.1 mmol/L), or lower concentrations associated with severe clinical or metabolic features. Patients under ten years or over 70 have increased risk of salicylate toxicity and may require dialysis at an earlier stage.

Paracetamol

Liver damage is possible in adults who have taken 10g or more of paracetamol. Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).

Risk Factors:

If the patient

a,    Is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.

Or

b,    Regularly consumes ethanol in excess of recommended amounts.

Or

c,    Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

Symptoms:

Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.

Management:

Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines, see BNF overdose section.

Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable) but results should not delay initiation of treatment beyond 8 hours after ingestion, as the effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Banimax is indicated for the short term treatment of mild to moderate pain, for example that associated with headache, toothache or injury and in the symptomatic relief of febrile illnesses, such as upper respiratory infection and influenza. This is a paracetamol/aspirin combination product. The paracetamol is in immediate release form while the aspirin is delayed release in order to reduce gastric irritation.

5.2 Pharmacokinetic properties

It has been demonstrated that micro-encapsulation of aspirin delays dissolution, thus minimising exposure of the gastric mucosa to acetyl salicylic acid and encouraging release in the small bowel; hence gastric irritation may be reduced. Although this increases the time for peak plasma concentration of acetyl salicylic acid to occur compared with that observed after administration of immediate release aspirin, it may result in more sustained analgesia if the total bioavailability of the drug is not reduced. In order to counter any delay in the onset of analgesia which may result from micro-encapsulation of the aspirin, immediate release paracetamol is included in the formulation.

5.3 Preclinical safety data

Acute Toxicity

Paracetamol hepatoxicity is directly dependent on the plasma concentration related to time. Plasma concentrations above 1.2 mmol/l at 4 hours. 0.6 mmol/l at 8 hours and 0.3 mmol/l at 12 hours are criteria for treatment with acetylcysteine to prevent irreversible liver damage.

Chronic Toxicity

In animal experiments the subchronic and chronic toxicity of paracetamol occurred in rats and mice as lesions in the gastro-intestinal tract, blood-count changes, degeneration and even necrosis of the hepatic and renal parenchyma. The metabolites that are assumed to have the toxic effects and the organic changes associated with them have been proven in humans as well.

Therefore, paracetamol should not be taken for a long period of time and in excessive doses. Oral daily doses with clearly hepatotoxic effects are around 5.8g for non-alcoholics, symptoms of intoxication can occur as soon as 3 weeks after administration.

Mutagenic and tumorigenic potential

In mammalian cell cultures paracetamol induces chromosome mutations depending on its concentration. In vivo tests show negative as well as slightly positive results. Due to the insufficient relevance of the most part of the in vivo tests no final evaluation is possible at this time.

Long-term studies in rats and mice have yielded no indications of a carcinogenic effect.

Reproductive toxicity

Paracetamol passes the placental barrier. Animal studies and experience to date in humans reveal no evidence of embryotoxicity.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Microcrystalline cellulose BP Sodium starch glycollate BP Sugar stearate E473 Quinoline yellow lake E104 Patent V blue lake E131 Polyethylene CIO

Incompatibilities

Not applicable.

6.3 Shelf life

36 months.

6.4 Special precautions for storage

Store in a dry place a temperature not exceeding 25°C, and protect from light.

6.5 Nature and contents of container

Blister packs in packs of 10.

6.6 Special precautions for disposal

The tablets should be swallowed whole and not broken or crushed.

7    MARKETING AUTHORISATION HOLDER

BRISTOL LABORATORIES LIMITED Unit 3, Canalside Northbridge Road,

Berkhamsted Herts HP4 1EG United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 17907/0292

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

06/03/2009

10    DATE OF REVISION OF THE TEXT

06/03/2009

11    DOSIMETRY (IF APPLICABLE)

12    INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS (IF APPLICABLE)